A member of the Coronaviridae family, Nidovirales order, and Coronavirus genus, bovine coronavirus (BCoV) is an enveloped, single stranded, nonsegmented, positive sense RNA virus that encodes: (i) a spike protein (S protein), which is a large surface glycoprotein that comprises an S1 domain and an S2 domain; (ii) a hemagglutinin-esterase protein (HE), (iii) an integral membrane protein (M); (iv) a small membrane protein (E); and (v) a nucleocapsid protein (N) [Fulton et al., Vaccine 31:886-892 (2013)]. BCoV was initially associated with a neonatal enteric disease in calves, as well as winter dysentery in adult cattle [Fulton et al., Vaccine 31:886-892 (2013)]. Subsequently, BCoV was implicated in respiratory infections in both recently weaned calves and feedlot calves [Plummer et al., JAVMA 225(5):726-731 (2004)]. Accordingly, BCoV has been found to be a pneumoenteric virus that can infect the intestine and upper and lower respiratory tract of cattle, with the bovine enteric coronavirus and the bovine respiratory coronavirus being reported to comprise only minor genetic differences. Consistently, there is an absence of any consistent antigenic or genetic markers that distinguish BCoV isolates according to their different clinical syndromes, as well as a report of a high level of cross-protection between bovine enteric coronavirus and the bovine respiratory coronavirus isolates following an in vivo challenge [Saif, Vet. Clin. North Am Food Anim Pract. 210(26):349-364 (2010)].
In addition, there are a significant number of other viruses and bacteria that can infect cattle. Viruses include bovine viral diarrhea virus types 1 and 2, (BVDV1, or alternatively BVD1; and BVDV2, or alternatively BVD2), infectious bovine rinotracheitis (IBR) virus, parainfluenza type 3 virus (PI3), bovine respiratory syncytial virus (BRSV), and Rift Valley fever virus (RVFV). Bacteria that can infect cattle include Pasteurella multocida, Mannheimia haemolytica, Histophilus somni, and Mycoplasma bovis. 
It is now widely accepted that the best way of preventing disease due to bacterial or virus infections in bovine is to vaccinate them against these pathogens. Moreover, multivalent live attenuated viral or bacterial vaccines can be safely administered that limit the number of vaccine injections required. Accordingly, multivalent live virus vaccines that protect against BVDV1 and BVDV2, IBR, PI3, and/or BRSV are commercially available. Surprisingly however, heretofore no commercial vaccines have contained a live attenuated bovine coronavirus that has been shown to aid in the protection against both respiratory disease and enteric disease caused by coronavirus. Therefore, there remains a need to obtain a bovine coronavirus suitable for a vaccine (or multivalent vaccine) to aid in the protection of calves and cattle from both respiratory infections and enteric infections due to BCoV.
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